Three scientists at Oregon Health & Science University have earned a substantial funding award to extend promising research to improve human health.
Recipients of the 2024 Faculty Excellence and Innovation Awards, made possible by the Silver Family Innovation Fund, include Angelica Morales, Ph.D., Arpiar “Arpy” Saunders, Ph.D., and Zheng Xia, Ph.D.
Each recipient receives a total of $750,000 over three years. The innovation fund is designed to buoy the next generation of faculty leaders at OHSU, so awardees are early- or mid-stage investigators of exceptional creativity and promise. This marks the fifth year since the annual awards began in 2020.
“This year’s awardees are highly creative and dedicated scientists who are committed to using new approaches to solve some of the most difficult challenges in medicine: substance use disorders, neurological conditions and cancer,” said Peter Barr-Gillespie, Ph.D., OHSU chief research officer and executive vice president. “Each of these scientists embody OHSU’s mission to improve the health and well-being of people in Oregon and beyond.”
OHSU deans, center and institute directors, and department chairs nominate candidates from their respective units, and applications are reviewed by prominent scientists across the country.
Angelica Morales, Ph.D.
Assistant professor of psychiatry in the OHSU School of Medicine
Angelica Morales, Ph.D., intends to apply the principals of precision medicine to a debilitating and commonplace health condition: Substance use disorders.
The award will enable Morales to greatly extend her previous research discerning the neurobiological basis of substance use and addiction in individuals. Morales specializes in using neuroimaging techniques to assess brain structure, function and chemistry that drives people to use, escalate and maintain their use of alcohol and other drugs.
The goal will be to match every individual to the intervention that’s most likely to work for them.
“Substance use disorders vary significantly from person to person, with individuals varying with respect to the combination of substances used, or in the presence of other mental health conditions,” Morales said.
The new funding will allow Morales to expand the collection of data and laboratory research, including brain imaging. Researchers will use that data to develop clinical trials matching individuals to a specific intervention based on their neurobiological profile.
Arpiar “Arpy” Saunders, Ph.D.
Assistant professor in the OHSU Vollum Institute
Arpiar “Arpy” Saunders, Ph.D., will use the Silver award to further the development of viral genomic technology, which seeks to map the intricate and vast network of synaptic connections between different cell types in large swaths of intact brain tissue.
These quantitative maps of synaptically connected cells — known as “connectomes” — are critical for every aspect of brain function. By making connectomes that are molecularly-informed and easy to generate, the Saunders lab will test hypotheses about how differences in neural wiring might drive neuropsychiatric disorders and contribute to unique capacities of the primate brain.
“Building connectomes is daunting yet critically important,” he said. “For example, emerging human genetic studies suggest mutations in synaptic proteins are major driving forces behind neurodevelopmental disorders. Building and comparing mutation-specific connectomes would thus accelerate insight-guided therapies to treat patient-specific ‘miswiring.’”
Saunders and his laboratory will use emerging tools in RNA imaging and engineered viral synaptic tracking devices to delineate individual parts of the connectome. Each part is a single “receiver” neuron associated with the hundreds of diverse “sender” neurons that directly feed synaptic information into that receiving cell. The whole connectome emerges through computational assembly of many thousands of these individual parts, involving millions of brain cells.
“The technology we are developing will allow us to generate extraordinarily data-rich descriptions of synaptic connectivity from the brains of individual animals,” Saunders said. “One important goal will be to work with Vincent Costa’s fantastic group at the Oregon National Primate Research Center to build primate connectomes. By mapping the synaptic specializations present in the primate brain, we hope to shed light on important cellular features that support human cognition.”
The funding will support the acquisition of an imaging rig and support for the scientists to generate and analyze the datasets. In collaboration with other OHSU researchers, Saunders hopes the project will further establish OHSU as a center for cutting-edge neural circuit analysis.
Zheng Xia, Ph.D.
Associate professor of biomedical engineering in the OHSU School of Medicine; member of the Center for Biomedical Data Science and OHSU Knight Cancer Institute
Zheng Xia, Ph.D., will use the award to develop the equivalent of ChatGPT for cancer.
He has already leveraged machine learning to analyze large-scale biomedical data to gain insights into the biological and clinical signals of aging, stem cells, neurological disorders and cancer, including more than 70 peer-reviewed scientific publications. His current research is single-cell data analysis, with recent high-profile publications in Nature Biotechnology, Nature and Nature Machine Intelligence.
The innovation award will enable him to leverage cutting-edge artificial intelligence, or AI, technologies to construct a foundation model by learning from millions of cells, which is commonly used in AI applications like ChatGPT. His lab will develop a transfer learning model capable of interpreting and analyzing single-cell RNA sequencing based on a catalogue extracted from 100 million cells and published research. He calls it “oncoGPT.”
This model will enhance downstream tasks that have limited sample sizes by leading to more accurate and robust predictions. It will facilitate the development of innovative treatment strategies for cancer patients while positioning OHSU at the forefront of AI-driven biomedical research.
“The system draws inspiration from the AI assistant J.A.R.V.I.S (Just a Rather Very Intelligent System) featured in the ‘Iron Man’ movie series,” he said. “We envision oncoGPT as an invaluable tool for scientists, empowering them to extract insights, generate hypotheses and develop advanced therapeutic strategies.”